rs2281525

Variant names:

• chr1-93129749-G-C
• rs2281525
• NM_007358.4:c.1160+301G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007358.4(MTF2):​c.1160+301G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,862 control chromosomes in the GnomAD database, including 30,458 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30458 hom., cov: 30)
• Consequence: MTF2 NM_007358.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 12 publications found

Genes affected

MTF2 (HGNC:29535): (metal response element binding transcription factor 2) Enables methylated histone binding activity and transcription corepressor binding activity. Predicted to be involved in several processes, including regulation of histone H3-K27 methylation; regulation of transcription by RNA polymerase II; and segment specification. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Located in cytoplasm; focal adhesion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTF2	NM_007358.4	c.1160+301G>C		intron_variant	Intron 11 of 14	ENST00000370298.9	NP_031384.1
MTF2	NM_001164392.2	c.989+2450G>C		intron_variant	Intron 10 of 13		NP_001157864.1
MTF2	NM_001164391.2	c.854+301G>C		intron_variant	Intron 12 of 15		NP_001157863.1
MTF2	NM_001164393.2	c.854+301G>C		intron_variant	Intron 9 of 12		NP_001157865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTF2	ENST00000370298.9	c.1160+301G>C		intron_variant	Intron 11 of 14	1	NM_007358.4	ENSP00000359321.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93516 AN: 151744 Hom.: 30462 Cov.: 30

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.658

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.616 AC: 93541 AN: 151862 Hom.: 30458 Cov.: 30 AF XY: 0.621 AC XY: 46076 AN XY: 74240

African (AFR) AF: 0.382 AC: 15804 AN: 41358

American (AMR) AF: 0.651 AC: 9934 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2491 AN: 3470

East Asian (EAS) AF: 0.702 AC: 3611 AN: 5144

South Asian (SAS) AF: 0.760 AC: 3664 AN: 4822

European-Finnish (FIN) AF: 0.758 AC: 8003 AN: 10556

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47792 AN: 67932

Other (OTH) AF: 0.656 AC: 1385 AN: 2110

Alfa AF: 0.645 Hom.: 4057

Bravo AF: 0.596

Asia WGS AF: 0.713 AC: 2478 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.44
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2281525; hg19: chr1-93595306;